Associations of longitudinal height and weight with clinical outcomes in pediatric kidney replacement therapy: results from the ESPN/ERA Registry.

BACKGROUND: Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. METHODS: We included patients < 20 years starting KRT in 33 European countries from 1995-2019 with height and weight data recorded to the ESPN/ERA Registry. We defined short stature as height standard deviation scores (SDS) < -1.88 and tall stature as height SDS > 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. RESULTS: We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78-0.86), tall (aHR: 0.65, 95% CI: 0.56-0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71-0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92-2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38-2.23) and obese (aHR: 1.49, 95% CI: 1.11-1.99) patients showed higher all-cause mortality risk than normal weight subjects. CONCLUSIONS: Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Enhancement of the antifungal activity of some antimycotics by farnesol and reduction of Candida albicans pathogenicity in a quail model experiment.

Background and Aim: Clinical strains of microorganisms, including pathogenic yeast-like fungi (YLF), are resistant to currently used antifungal agents. Thus, it is relevant to study the combinations of existing antimicrobial drugs and a medicinal extract of plant origin (farnesol). In previous studies, farnesol showed a relatively strong anti-biofilm effect against Candida albicans. This study aimed to determine how much the resistance profile of non-biofilm microorganisms can change. Materials and Methods: Six clinical isolates of C. albicans and one reference strain were used to study the interaction of farnesol with the most used antimycotics. To determine the sensitivity of YLF to antimycotic drugs, such as nystatin (50 µg), amphotericin B (10 µg), ketoconazole (10 µg), clotrimazole (10 µg), voriconazole (10 µg), fluconazole (25 µg), miconazole (10 µg), and intraconazole (10 µg), the classic disk diffusion method was used. In the second stage, one of the six strains was used to simulate candidiasis of the gastrointestinal tract in an in vivo quail model. As an unusual experimental design, this study investigated the effects of pretreated C. albicans in quails, not the in vivo pathogenicity of C. albicans, after treatment with farnesol. Results: The resistance profiles of Candida strains did not improve with farnesol in all strains. All concentrations of farnesol (100, 50, and 25 µM) demonstrated a fungistatic effect (i.e., an increase in drug sensitivity) in 23 of 56 (7×8) cases (41%). The remaining 54% demonstrated no changes in the resistance to antifungal drugs or deterioration of the indicators in rare cases (5%). At 100 µM farnesol, sensitivity improved in 33 of 56 cases (59%). Candidiasis or the severity of clinical disease of the quail digestive tract developed to a lesser extent if fungi were treated with farnesol. Conclusion: Farnesol does not always show a positive result on single cells without biofilm in the laboratory. However, in a biofilm or an in vivo model with biofilms, farnesol can be considered a new antimycotic drug or an additive to existing antimycotics.

Reduction in Pathogenicity in Yeast-like Fungi by Farnesol in Quail Model.

Candida albicans was the first eukaryotic microorganism to exhibit quorum-sensing through the secretion of the sesquiterpene E, farnesol. This molecule is generated by dephosphorylation of farnesyl pyrophosphate in the mevalonate biosynthetic pathway in mammalian and yeast cells. Exogenous farnesol inhibits yeast-to-hyphal formation in a concentration- and time-dependent manner at the earliest stage of hyphal development. Much research has been devoted to studying the role of farnesol as an inhibitor of hyphal morphogenesis; however, little research has been published regarding the in vivo impacts of farnesol on fungal virulence and the development of Candida infection. While other studies have examined the impact of multiple doses of farnesol in addition to antimycotics, we hypothesize that C. albicans treated with a single dose of this quorum-sensing molecule could reduce fungal virulence in a quail model.

Fecal Microbiota Analysis in Cats with Intestinal Dysbiosis of Varying Severity.

Recent studies have shown that the gut microbiota plays an important role in the pathogenesis of gastrointestinal diseases in various animal species. There are only limited data on the microbiome in cats with varying grades of dysbiosis. The purpose of the study was a detailed analysis of the quantitative and qualitative fecal microbiota spectrum in cats with intestinal dysbiosis of varying severity. The data obtained indicate that, depending on the dysbiosis severity in cats, the intestinal microbiome landscape changes significantly. It has been established that, depending on the dysbiosis severity, there is a shift in the balance between the Gram-positive and Gram-negative bacterial pools and in the nature of the isolation of specific bacteria forms, in the amount of obligate microbiota isolation, as well as individual facultative strains. When analyzing the serotyping of E. coli cultures isolated at various grades of intestinal dysbiosis severity, differences were found both in the isolation amount of various serotypes from one animal and in the prevalence of certain serotypes for each disease severity. A retrospective analysis of the fecal microbiota sensitivity in cats with dysbiosis to antibacterial drugs showed that, depending on the disease severity, the number of isolates sensitive to antibiotics increases significantly.

Growth Patterns After Kidney Transplantation in European Children Over the Past 25 Years: An ESPN/ERA-EDTA Registry Study.

BACKGROUND: Improved management of growth impairment might have resulted in less growth retardation after pediatric kidney transplantation (KT) over time. We aimed to analyze recent longitudinal growth data after KT in comparison to previous eras, its determinants, and the association with transplant outcome in a large cohort of transplanted children using data from the European Society for Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry. METHODS: A total of 3492 patients transplanted before 18 years from 1990 to 2012 were included. Height SD scores (SDS) were calculated using recent national or European growth charts. We used generalized equation models to estimate the prevalence of growth deficit and linear mixed models to calculate adjusted mean height SDS. RESULTS: Mean adjusted height post-KT was -1.77 SDS. Height SDS was within normal range in 55%, whereas 28% showed moderate, and 17% severe growth deficit. Girls were significantly shorter than boys, but catch-up growth by 5 years post-KT was observed in both boys and girls. Children <6 years were shortest at KT and showed the greatest increase in height, whereas there was no catch-up growth in children transplanted >12. CONCLUSIONS: Catch-up growth post-KT remains limited, height SDS did not improve over time, resulting in short stature in nearly half of transplanted children in Europe.

Mineral metabolism in European children living with a renal transplant: a European society for paediatric nephrology/european renal association-European dialysis and transplant association registry study.

BACKGROUND AND OBJECTIVES: Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study included 1237 children (0-17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure. RESULTS: Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR. CONCLUSIONS: Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction.